TALE and TALEN genome editing technologies

• TALE and TALEN technology is evolving to new functionalities. • TALE nucleases, activators, transposases, recombinases, epigenomic modifiers, and base editors. • Guidelines for TALEN design. • Agronomical and medical achievements of TALEN. TALEN were the first easy-to-use genome editing technology and sparked the genome editing revolution. Their application in multiple species brought targeted mutagenesis to the attention of scientists worldwide. Key breakthrough successes of genome editing have since been achieved using TALEN, among these, the first commercialization of an edited crop and the first human cured from cancer. TALEN have since been largely replaced by the CRISPR technologies which are somewhat easier to build, much easier to multiplex, and have spawned multiple derived techniques. Nevertheless, the flexible and precise positioning of TALEN is unmatched, and thus they have continued to evolve to new functionalities. Here, we assemble essential facts, design guidelines as well as important past and exciting novel developments.